Enhanced Glucose Tolerance in Spontaneously Hypertensive Rats: Pancreatic β-Cell Hyperfunction With Normal Insulin Sensitivity

Buchanan, Thomas A.; Youn, Jang H.; Campese, Vito M.; Sipos, George F

doi:10.2337/diab.41.7.872

Cited by 45 publications

(19 citation statements)

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“…In the present study, we confirmed the results of previous studies [14,15] In addition, a decrease in blood pressure in SHR was not always associated with a reduction in plasma insulin concentrations.…”

Section: Discussionsupporting

confidence: 82%

A Study of Effect of CS-045, a New Antidiabetic Drug, on Hypertension in Spontaneously Hypertensive Rat.

1995

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Abstract.Several lines of evidence have suggested that insulin resistance may play an important role in the pathogenesis of hypertension. CS-045 is a new hypoglycemic drug by which improves insulin sensitivity in peripheral tissues.We assessed the effect of CS-045 on hypertension in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) as a control. At 20 weeks of age, the treatment with CS-045 was started by being mixed with chow pellets in the proportion of 0.2% (w/w) and continued for 6 weeks. Nonfasting plasma glucose levels were not changed in either strain of rats treated with CS-045, but plasma insulin levels decreased in SHR 4 and 5 weeks after the start of CS-045 therapy.Blood pressure increased with age in SHR without treatment, but CS-045 decreased blood pressure only 4 and 6 weeks after the treatment. These findings suggest that insulin resistance is not strongly associated with the pathogenesis of hypertension in SHR.

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Section: Discussionsupporting

confidence: 82%

A Study of Effect of CS-045, a New Antidiabetic Drug, on Hypertension in Spontaneously Hypertensive Rat.

1995

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“…Some studies showed a reduction of glucose tolerance and insulin action (18,21,29,38). On the contrary, in other studies, an increased insulin sensitivity (17,49) or no evidence of insulin resistance (7,8,17) has been observed in SHR. To clarify these contradictions, more recently, we applied the minimal model of glucose kinetics to insulinemia and glycemia data obtained from IVGTT to test whether high blood pressure causes reductions of S I and S G indexes in the SHR similar to those observed in hypertensive humans (32).…”

Section: Discussionmentioning

confidence: 83%

Enhanced sympathetic reactivity associates with insulin resistance in the young Zucker rat

Ruggeri¹,

Brunori²,

Cogo³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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Somatosympathetic reflexes were studied in young hyperinsulinemic, insulin-resistant (Zucker fatty) rats (ZFR) and a related control (Zucker lean) strain (ZLR). Glucose metabolism was characterized by minimal model analysis of intravenous glucose tolerance test data. Seven-week-old ZFR (n ϭ 18) and ZLR (n ϭ 17) were studied under pentobarbital anesthesia. Mean body weight and plasma glucose and insulin concentration were significantly greater (P Ͻ 0.05) in ZFR than in ZLR, whereas basal values of mean arterial pressure (MAP) and heart rate (HR) were not significantly different. Increments of MAP (⌬MAP) and HR (⌬HR) elicited by electrical stimulation of the sciatic nerve (5-s trains of 100 pulses, 0.5-ms pulse duration, 100-to 400-A pulse intensity) were significantly higher (ANOVA, P Ͻ 0.05) in ZFR at each level of stimulus intensity. Regression analysis showed a linear increase in ⌬MAP and ⌬HR with increasing sciatic nerve stimulus intensity. Pressor responses to phenylephrine after ganglionic blockade demonstrated that vascular reactivity to adrenergic stimulation is not increased in ZFR compared with ZLR. Thus this factor does not contribute to enhancement of somatosympathetic reflexes observed in this strain. Insulin sensitivity in ZFR was onefourth (P Ͻ 0.05) that in ZLR. These results suggest that stronger sympathetic nervous reactivity in ZFR is associated with a severe insulin-resistant state before the onset of hypertension and support the hypothesis that insulin-mediated stimulation of the sympathetic nervous system is involved in the development of cardiovascular diseases related to alterations of glucose metabolism. sympathetic nervous activity; minimal model analysis; glucose kinetics; hypertension HYPERINSULINEMIA AND INSULIN resistance are considered important risk factors for development of hypertension (2, 39), and a number of studies have shown a significant association between hypertension and insulin resistance in obese and nonobese individuals (12,15,27,28,46). However, the pathophysiological relation among hyperinsulinemia, insulin resistance, and hypertension remains poorly understood.Some experimental reports suggest that an increase in sympathetic nervous system activity (SNA) may play a role in the association between insulin resistance and elevated blood pressure (39). This association might be due to a primary increase in sympathetic activity (22). Although an increase in sympathetic activity can cause hypertension and insulin resistance, studies performed on animal models indicate that the insulin resistance induced by a high-lipid diet occurs before the onset of hypertension (20), suggesting the primacy of the insulinmediated stimulation of the sympathetic nervous system. If this is true, a suitable animal model to investigate the mechanisms underlying insulin resistance and its associated pathologies is the obese Zucker rat, homozygous for the fa allele (fa/fa), in which a mutation of the leptin receptor-coding gene impairs the ability of leptin to suppress food intake. Homozygous ...

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“…15 Although a few recent studies do not support the presence of insulin resistance in the SHR, 1617 the presence of hyperinsulinemia was confirmed even in those studies. 16 It has been suggested that nutrientstimulated hyperinsulinemia may play a role in the development of high BP in the SHR. 16 If this hypothesis were valid, then a drug intervention that decreases plasma insulin levels in the SHR should also lower BP.…”

Section: Sanjay Bhanot John H Mcneillmentioning

confidence: 99%

“…16 It has been suggested that nutrientstimulated hyperinsulinemia may play a role in the development of high BP in the SHR. 16 If this hypothesis were valid, then a drug intervention that decreases plasma insulin levels in the SHR should also lower BP. Previous studies from our laboratory have shown that vanadyl, the ( + IV) form of the trace element vanadium, exhibits effects on carbohydrate metabolism that are very similar to those of insulin.…”

Section: Sanjay Bhanot John H Mcneillmentioning

confidence: 99%

Vanadyl sulfate lowers plasma insulin and blood pressure in spontaneously hypertensive rats.

Bhanot

McNeill

1994

Hypertension

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Spontaneously hypertensive rats (SHR) are hyperinsulinemic compared with their Wistar-Kyoto (WKY) controls. Since previous studies have demonstrated that vanadyl sulfate lowers insulin levels in nondiabetic rats, we used vanadyl to explore the relation between hyperinsulinemia and hypertension. In a prevention study, 5-week-old SHR and WKY rats were started on long-term vanadyl sulfate treatment. Vanadyl in doses of 0.4 to 0.6 mmol/kg per day lowered plasma insulin (252±22.8 versus 336±12.6 pmol/L, treated versus untreated, P<.01) and systolic blood pressure (158±2 versus 189±1 mm Hg, P<.001) in SHR without causing any change in plasma glucose. No changes were seen in the treated WKY rats. At 11 weeks of age, a group of untreated rats from the prevention study was started on vanadyl treatment as before. Again, vanadyl caused significant and sustained decreases in plasma insulin (264±12.6 versus 342±6.6 pmol/L, treated versus untreated, P<.001) and blood pressure (161 ±1 versus E ssential hypertension is associated with multiple metabolic defects in carbohydrate and lipoprotein metabolism 13 that include insulin resistance, hyperinsulinemia, and dyslipidemia.1 ' 45 Insulin resistance in hypertension is often accompanied by hyperinsulinemia, 67 and these metabolic defects persist when blood pressure (BP) is reduced by conventional antihypertensive drugs.58 Hyperinsulinemia in hypertension is probably a reflection of the resistance to the peripheral uptake and utilization of glucose, with high levels of insulin needed to maintain and/or sustain euglycemia in the presence of insulin resistance.9 -10 However, the precise nature of this relation remains unexplained. The primary question that needs resolution is whether or not these defects in carbohydrate metabolism are causally related to hypertension.Insulin resistance and hyperinsulinemia have also been documented in three models of experimental hypertension 1114 including the genetically predisposed spontaneously hypertensive rat (SHR).13 Furthermore, SHR exhibit a decreased insulin clearance, which may also result in increased plasma insulin

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Enhanced Glucose Tolerance in Spontaneously Hypertensive Rats: Pancreatic β-Cell Hyperfunction With Normal Insulin Sensitivity

Cited by 45 publications

References 0 publications

A Study of Effect of CS-045, a New Antidiabetic Drug, on Hypertension in Spontaneously Hypertensive Rat.

A Study of Effect of CS-045, a New Antidiabetic Drug, on Hypertension in Spontaneously Hypertensive Rat.

Enhanced sympathetic reactivity associates with insulin resistance in the young Zucker rat

Vanadyl sulfate lowers plasma insulin and blood pressure in spontaneously hypertensive rats.

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